The suicide rate in the USA is the same as 60 years ago. Better prevention needs more data on risk and resilience biomarkers. We seek to determine both resilience and vulnerability potential endophenotypes for suicide attempts in major depressive disorder (MDD). Both endophenotypes may aid estimation of risk and provide new targets for prevention intervention. The study design compares healthy volunteers (Group 1) with medication-free adult offspring of a parent with MDD and suicidal behavior who are through the age of risk and can thus be divided into a resilient group (Group 4), a group with a diathesis for MDD (Group 2) and one with diatheses for MDD and suicide attempts (Group 3). Comparison of Groups 2 and 3 indicates the diathesis for suicidal behavior. Comparison of Group 1 and 4 indicates the resilience phenotype. Comparison of Group 1 and Group 2 indicates the diathesis for MDD. This study is a new direction based on our almost complete longitudinal two-site follow-up study (PI, J. John Mann, MD, MH056390, Columbia University, NYC and PI, David Brent, MD, MH056612, UPMC, Pittsburgh) of 701 offspring of 334 probands with mood disorder entitled: Familial Pathways to Early-Onset Suicide Attempts that has sought to identify mechanisms by which suicidal behavior risk is transmitted from parent to offspring. Our findings on risk traits in the domains of cognition, mood regulation and stress responses, together with a new domain of brain PET imaging of the 5-HT1A autoreceptor that regulates serotonin release, will focus the search for resilience and vulnerability phenotypes. This study will involve the same two performance sites as the current funded application that ends January 2015. The teams have worked together for >15 years and both teams have conducted PET studies of depressed and suicidal patients. We will recruit eligible offspring from the old study and recruit new offspring as needed for the four groups. Both sites will perform clinical and cognitive assessments, stress tests and PET/MRI scans using identical protocols. The New York site will be the data management site including image analyses and statistics, and assay cortisols.